Copper-Catalyzed Asymmetric Hydroaminocarbonylation of Unactivated Internal Alkenes

The catalytic production of chiral amides from readily available unactivated internal alkenes remains a significant challenge in synthetic chemistry. In this work, we developed a highly enantioselective hydroaminocarbonylation procedure for nonactivated internal alkenes and a wide range of alpha-chiral amides were produced effectively with exceptional enantioselectivities using copper as the catalyst. This method is compatible with both symmetric and asymmetric internal alkenes, as well as various hydroxylamine electrophiles, demonstrating wide substrate scope and broad functional group tolerance. The established catalytic system showcases remarkable enantioselective performance in the asymmetric hydroaminocarbonylation of challenging substrates, such as the methyl-ethyl alpha-chiral amide synthesis from trans-2-butene, despite the minimal steric difference between the methyl and ethyl group. This work represents important progress in the field of asymmetric hydroaminocarbonylation and offers a useful tool for the production of valuable alpha-chiral amide compounds from readily available internal alkenes.